Papillary thyroid carcinoma in a hyperfunctioning autonomous nodule: A diagnostic paradox challenging clinical guidelines

Background: Papillary thyroid carcinoma (PTC) is rarely found within hyperfunctioning (hot) thyroid nodules, which are typically considered benign. This case challenges the prevailing notion that functional autonomy excludes malignancy and underscores the need for a nuanced diagnostic approach. Methods: We report the case of a 63-year-old woman with clinical hyperthyroidism and a palpable right thyroid nodule. Biochemical tests confirmed thyrotoxicosis (TSH <0.005 µIU/mL, free T4 25.55 pmol/L and T3 7.69 pmol/L). Despite the hyperfunctioning profile, thyroid ultrasound showed high-risk features, including hypoechogenicity, microcalcifications, irregular margins, and elevated stiffness on shear wave elastography, classifying the lesion as ACR-TIRADS 5. A 99mTc scan confirmed a hyperfunctioning nodule. Fine-needle aspiration cytology (FNAC) revealed PTC. She subsequently underwent total thyroidectomy. Results: FNAC revealed PTC. Histopathology confirmed a 13 mm intrathyroidal papillary carcinoma with mixed classic (40%) and oncocytic (60%) subtypes, without capsular or extrathyroidal extension. The background thyroid tissue showed macrofollicular hyperplasia. The patient recovered uneventfully and did not require radioactive iodine ablation. Genetic testing was unavailable. Conclusion: This case illustrates that malignancy can coexist with hyperfunctioning thyroid nodules. Suspicious sonographic features should not be dismissed due to functional status. Cytological evaluation remains essential when ultrasound findings raise concern, supporting a shift toward integrated diagnostic decision-making in thyroid nodule assessment.